Our report is the first to describe the outcome of two patients with severe infections due to Gram-negative bacteria that involved non-removable intravascular devices. In both cases, treatment with combined regimens with cefiderocol was successful and no implant removal was necessary. A recent study using a worldwide collection of 8954 clinical isolates of Pae, Enterobacteriaceae, Acinetobacter baumannii, Stenotrophomonas maltophilia and Burkholderia cepacia, collected from 2015 to 2016, revealed that cefiderocol demonstrated potent in vitro activity (MIC ≤ 4 mg/L) against the majority (99.4%) of these isolates, including MDR strains [8, 13].
We assumed that both patients presented with intravascular device-associated infection, given bacteremia persistence and in spite of correct antibiotic administration per in vitro-tested susceptibilities and no other secondary foci. Cefiderocol may have had a role in both cases. In the first case, the role of cefiderocol may be less relevant, as blood cultures tested negative upon drug initiation. However, there was a clinical and analytical improvement, such as the rapid CRP decrease after administration of the drug. As this patient continues receiving suppressive therapy with oral minocycline 100 mg/12 h, it is not possible to confirm a complete cure of the infection. However, the commonly reached serum concentration of minocycline is < 2 mg/L and the MIC of this drug for this strain was 3 mg/L. Its activity may have therefore been only partial, which makes it difficult to assume that minocycline alone is controlling the infection.
Cefiderocol has also been reported in recent cases of intravascular devices/infections. Trecarichi et al. reported a case of XDR-A. baumannii-causing pneumonia and bloodstream infection in a patient on extracorporeal membrane oxygenation[14]. Furthermore, a separate, recent report of endocarditis due to XDR-Pae was successfully treated with cefiderocol[15]. Although the patient underwent aortic valve surgery after six doses of cefiderocol, the valve culture was negative. Thus, cefiderocol may have potential activity against biofilm-forming Gram-negative pathogens, which are eager to capture iron. Infected devices should be removed whenever possible. When removal cannot be achieved, antimicrobials retaining anti-biofilm activity should be prioritized. A recent report suggests that cefiderocol may reduce biofilm and may inhibit planktonic growth of Gram-negative bacteria [16].
Patients in our first case and in that reported by Edgeworth et al. developed thrombocytopenia and neutropenia, respectively. Interestingly, both patients received cefiderocol and a second beta-lactam (piperacillin-tazobactam and meropenem, respectively) for ≥ 2 weeks. Important side effects of this kind have never been described in the literature.
In conclusion, in challenging MDR and XDR Gram-negative infections, cefiderocol may be an additional, promising drug to the therapeutic options available for clinicians, even in cases of difficult-to-treat, intravascular foreign body infections with non-removable devices.